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Resistance
Jun 25, 2006

I had been on T20 for one year and on a CCR5 inhibitor for 1 month without liver problems..I was doing very well on the CCR5 inibitor; however, they have now stopped it my virus appears to have gone from CCR5 to CXCR4 receptor utilizing.. My Dr said that I have not developed any new mutations Could that be true? My T-cells are 40 and viral load 65,000. Should I start TMC 114 and TMC 125 or TMC 278? thank you.. Toronto Canada

Response from Dr. Daar

Hi Toronto Canada,

I probably do not have all the information I need in order to answer your questions, but will try to share with you some general thoughts.

I assume that you were on a combination of traditional antiretrovirals (e.g. NRTIs and PIs) along with T20 and an investigational CCR5 inhibitor. It would be useful to know what your viral load was on this regimen as well as how you tolerated this the medications. I would also be interested to know which of these were stopped, i.e. all of your meds or just the CCR5 inhibitor, and why.

Most studies thus far with CCR5 inhibitors have enrolled those without detectable strains that use the CXCR4 co-receptor (X4 viruses) since the CCR5 inhibitor does not prevent infection by these strains. One concern is that in those using CCR5 inhibitors virus will develop or emerge that use the other receptor. Based upon what you have written it appears that this might be what has occurred in your case. Alternatively, we have learned from experience that there are some people who initially have undetectable X4 virus and then on repeat testing these strains are detectable even with the introduction of any therapy. Some of this may simple reflect limitations of the currently available assays. Clearly more information about these issues will emerge as co-receptor inhibitors move forward in clinical trials.

What you should do next is a tough one and requires much more detailed information regarding your treatment history as well as current and past resistance testing. Obviously with a T cell count of 40 it would be ideal if you could be placed on a highly effective regimen. Determining whether this is possible and which drugs to use would require more detailed discussion with your provider who has access to more information about your treatment history. Certainly the investigational drugs you list are often options for treatment-experienced subjects, but they are not for everyone. This is what needs to be sorted out with your primary provider.

Best, Eric


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